Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2025 Jun 24:13:1632122.
doi: 10.3389/fcell.2025.1632122. eCollection 2025.

Interactions between glioblastoma and myeloid cells

Yuting Li  1   2 , Yuhong Chen  3 , Kai Cai  1   2 , Yujuan Qin  4 , Xi Wang  5 , Bo Zhang  4 , Lin Shi  4 , Zonglin He  1   2 , Jiasheng Wang  1   2 , Jiecun Long  1   2 , Yishun Zeng  1   2 , Qiong Gong  1   2
Affiliations
Review

Interactions between glioblastoma and myeloid cells

Yuting Li et al. Front Cell Dev Biol. .

Abstract

Standing as the most aggressive form of primary malignant tumor, Glioblastoma (GBM) tumors with marked heterogeneity represents one of the enormous challenges in glioma treatment. Myeloid cells, which includes neutrophils, myeloid-derived suppressor cells, microglia, and macrophages, play a pivotal role in the tumor microenvironment of GBM. In the tumor microenvironment (TME), T cells and natural killer (NK) cells exert anti-tumor functions, whereas myeloid-derived suppressor cells (MDSCs) can promote tumor progression by suppressing these immune responses. Therefore, MDSCs play a critical role in shaping the effectiveness of immunotherapy. TME has constrained the ability of traditional GBM treatment approaches to significantly enhance prognostic outcomes for patients. This category encompasses conventional therapies like surgical resection and radiation therapy, along with cutting-edge methodologies such as immunotherapy. Through extensive investigations into the dynamic interactions between the GBM microenvironment and neoplastic cells, both targeted treatment strategies and innovative immunotherapeutic modalities have emerged, offering promising new directions for clinical intervention. This review focuses on the interactions between GBM and myeloid cells (MCs), providing novel insights into the oncogenesis and progression of GBM.

Keywords: GBM; MDSC; TAM; TME; myeloid cells.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Interactions Between GBM and Myeloid Cells. During GBM progression, tumour cells secrete cytokines and chemokines (e.g., CCL2, CXCL12, CSF-1, VEGF) that recruit myeloid cells including monocytes, neutrophils, and MDSCs. Distinct TAM subpopulations with specific gene signatures have been identified, such as microglia-like, hypoxic, and phagocytic macrophages. TAM-derived CCL2 recruits CCR2+Ly6C+ monocytic MDSCs, enhanced by tumour factors like osteoprotegerin, promoting immunosuppression. Myeloid cells suppress anti-tumour immunity via cytokines (TGF-β, IL-10) and chemokines (CCL2, CXCL12), facilitating GBM immune evasion.
FIGURE 2
FIGURE 2
Spatial Relationships Among Different Cell Types in GBM Microglia and macrophage populations tend to exhibit spatial segregation. Macrophages are more likely to cluster with each other and remain distant from microglia, while microglia are enriched near other microglia and avoid macrophages. However, some myeloid cell subpopulations—such as TAM-Cd68, TAM-Int, and Mg-like cells—are distributed more randomly and evenly throughout the tumor microenvironment, showing minimal distance differences relative to other cell types. Macrophages tend to cluster in regions with high tumor cell density and phenotypic diversity, where they interact with various non-myeloid cell types. Almost all myeloid populations show a significantly higher proportion of interactions with core tumor cells, as well as increased interactions with glial cells located at the tumor margin.
FIGURE 3
FIGURE 3
The relevant cellular interactions.
See this image and copyright information in PMC

References

    1. Abdelfattah N., Kumar P., Wang C., Leu J. S., Flynn W. F., Gao R., et al. (2022). Single-cell analysis of human glioma and immune cells identifies S100A4 as an immunotherapy target. Nat. Commun. 13 (1), 767. 10.1038/s41467-022-28372-y - DOI - PMC - PubMed
    1. Atai N. A., Bansal M., Lo C., Bosman J., Tigchelaar W., Bosch K. S., et al. (2011). Osteopontin is up-regulated and associated with neutrophil and macrophage infiltration in glioblastoma. Immunology 132 (1), 39–48. 10.1111/j.1365-2567.2010.03335.x - DOI - PMC - PubMed
    1. Bae E., Huang P., Müller-Greven G., Hambardzumyan D., Sloan A. E., Nowacki A. S., et al. (2022). Integrin α3β1 promotes vessel formation of glioblastoma-associated endothelial cells through calcium-mediated macropinocytosis and lysosomal exocytosis. Nat. Commun. 13 (1), 4268. 10.1038/s41467-022-31981-2 - DOI - PMC - PubMed
    1. Bayik D., Zhou Y., Park C., Hong C., Vail D., Silver D. J., et al. (2020). Myeloid-derived suppressor cell subsets drive glioblastoma growth in a sex-specific manner. Cancer Discov. 10 (8), 1210–1225. 10.1158/2159-8290.CD-19-1355 - DOI - PMC - PubMed
    1. Bian Z., Abdelaal A. M., Shi L., Liang H., Xiong L., Kidder K., et al. (2018). Arginase-1 is neither constitutively expressed in nor required for myeloid-derived suppressor cell-mediated inhibition of T-cell proliferation. Eur. J. Immunol. 48 (6), 1046–1058. 10.1002/eji.201747355 - DOI - PMC - PubMed

LinkOut - more resources